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CD34+ progenitor cells from asymptomatic patients are not a major reservoir
for human immunodeficiency virus-1
TF Neal, HK Holland, CM Baum, F Villinger, AA Ansari, R Saral, JR Wingard and WH Fleming
Department of Medicine, Emory University, Atlanta, GA 30322, USA.
Controversy exists as to whether hematopoietic progenitor cells are
infected by human immunodeficiency virus-1 (HIV-1) in vivo. Most studies
have focused on patients with acquired immunodeficiency syndrome
(AIDS)/AIDS-related complex, and little data are available on asymptomatic
patients with well preserved CD4+ T-cell counts. To determine if CD34+
hematopoietic progenitor cells are infected early in the course of HIV-1
disease, we evaluated 10 asymptomatic HIV-1 seropositive (HIV-1+) patients.
The CD34+ cell fraction was purified by a two-step procedure consisting of
both affinity chromatography and fluorescence-activated cell sorting that
resulted in a median purity of over 99%. Using conventional and nested
polymerase chain reaction (PCR) assays, we evaluated the presence and
frequency of HIV-1 proviral DNA. Both bone marrow mononuclear cells and
CD34- cells from all 10 patients were strongly positive for the HIV-1 pol
and/or gag gene sequences. In contrast, sorted CD34+ cells from only two of
10 patients were positive, and the number of copies of proviral DNA in
these samples was estimated to be from 2 to 5 per 250,000 cells. To test
the in vitro functional capacity of CD34+ progenitors, these cells were
assayed in both methylcellulose and long-term stromal culture. We found no
significant reduction in the number of colony-forming unit-erythroid
(CFU-E), burst-forming unit-erythroid (BFU-E), or colony-forming unit-
granulocyte macrophage (CFU-GM) colonies, or in the frequency of
cobblestone area forming cells from limit dilution analysis in HIV-1+
asymptomatic patients. Pooled methylcellulose colonies generated from CD34+
cells were HIV-1- in nine of 10 samples. All progeny from long- term
cultures of CD34+ cells were HIV-1-. We conclude that the CD34+
hematopoietic progenitor compartment is not infected in the majority of
asymptomatic HIV-1+ patients, and that these cells may represent a suitable
target for strategies designed to protect developing CD4+ T cells from
infection.
Volume 86,
Issue 5,
pp. 1749-1756,
09/01/1995
Copyright © 1995 by The American Society of Hematology
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